PDF(Pubmed)
Abstract：
Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.
摘要：
最近,环境温度已被证明可以调节骨骼稳态。然而,冷暴露影响骨量的机制尚不清楚。在我们目前的研究中，我们观察到暴露于低温（CT）会降低小鼠的骨量和质量。此外，来自暴露于低温的小鼠血浆的外泌体的移植（CT-EXO）也可以损害BMSCs的成骨分化，并通过抑制自噬活性来降低骨量。雷帕霉素,一种有效的自噬诱导剂，可以逆转冷暴露或CT-EXO诱导的骨丢失。微阵列测序显示冷暴露增加了CT-EXO中的miR-25-3p水平。机制研究表明miR-25-3p可抑制BMSCs的成骨分化和自噬活性。结果表明，抑制外泌体释放或下调miR-25-3p水平可以抑制CT诱导的骨丢失。这项研究确定了CT-EXO通过miR-25-3p通过靶向SATB2抑制自噬来介导CT诱导的骨质疏松效应，提出了低温对骨量影响的新机制。
